May 30, 2013 (NOT-OD-13-074) -
NIH to Require Use of Updated Electronic Application Forms for Due Dates on or after September 25, 2013. Forms-C applications are required for due dates on or after September 25, 2013.

This FOA provides for grant applications for
investigator-initiated, multi-center clinical studies. NIDDK supports
investigator-initiated, multi-center clinical studies through a two-part
process that includes an implementation planning grant (U34; see PAR-10-197).
NIDDK will accept, peer review and consider for funding applications for
investigator-initiated, multi-center clinical studies only from U34 grant
awardees, except in cases where an exemption from the requirement has been
given by NIDDK. Completion of the required products of a U34 grant is a
prerequisite for submission of a multi-center clinical cooperative agreement
(U01) application under this FOA.

Key Dates

Posted Date

March 16, 2011

Open Date (Earliest Submission Date)

May 5, 2011

Letter of Intent Due Date

Not Applicable

Application Due Date(s)

Standard
dates apply, by 5:00 PM local time of applicant organization.

AIDS Application Due Date(s)

Standard
dates apply, by 5:00 PM local time of applicant organization.

It is critical that applicants follow the instructions in
the SF
424 (R&R) Application Guide except where instructed to do otherwise (in
this FOA or in a Notice from the NIH Guide for Grants and Contracts).
Conformance to all requirements (both in the Application Guide and the FOA)
is required and strictly enforced. Applicants must read and follow all
application instructions in the Application Guide as well as any
program-specific instructions noted in Section
IV. When the program-specific instructions deviate from those in the
Application Guide, follow the program-specific instructions. Applications that
do not comply with these instructions may be delayed or not accepted for review.

As announced in NOT-DK-07-015,
and clarified in NOT-DK-10-003,
NIDDK will support investigator-initiated, multi-center clinical studies
through a two part grant process: (1) implementation planning (U34) grant
followed by (2) multi-center clinical study cooperative agreement (U01). PAR-10-197,
NIDDK MULTI-CENTER CLINICAL STUDY IMPLEMENTATION PLANNING (U34) GRANTS,
addresses the U34 grant; this PAR, NIDDK MULTI-CENTER CLINICAL STUDY
COOPERATIVE AGREEMENTS (U01), addresses the second part of the grant process.

This
policy applies to all clinical studies, interventional trials as well as
observational studies, conducted at three or more centers.
NIDDK will not accept applications for multi-center clinical studies that are
submitted as R01s, with the exception of ancillary studies to existing cooperative
agreements, which can be submitted as R01s to PAR-09-247: Ancillary Studies to
Major Ongoing Clinical Research Studies to Advance Areas of Scientific Interest
within the Mission of the NIDDK (R01) (https://grants.nih.gov/grants/guide/pa-files/PAR-09-247.html),
or applications submitted in response to other or future NIDDK FOAs that allow
multi-center applications. This policy does not apply to pilot studies.
Investigators who are interested in obtaining support for pilot studies may use
the R21 mechanism, through the appropriate program announcements.

Overview of the NIDDK policy for investigator-initiated,
multi-center clinical studies

Part 1. Implementation Planning (U34) Grant. NIDDK will
support clinical study planning (U34) grants for multi-center clinical studies.
These grants are intended to support all administrative study group activities
that are required in order to begin recruitment of subjects. These activities
include, but are not limited to: establishing the research team, developing
tools for data management and oversight of the research, defining recruitment
strategies, finalizing the protocol and investigators brochure, writing of the
Manual of Operations, establishing a data and safety monitoring plan, and
initiating the IRB approval process. The
U34 is not designed for the collection of preliminary data, for the conduct of
pilot and feasibility studies to support the rationale for a clinical study, or
for designing the study. The U34 application must include the proposed study
design and a full protocol.

All applications for multi-center clinical studies must
complete this two-part process, unless an exemption from this requirement has
been obtained from NIDDK. The U34 grant will provide up to two years of
support. U34 applications will be peer reviewed by special emphasis panels
convened by the NIDDK Review Branch.

The product of an awarded and successful U34 will be an
application to conduct the clinical study. It is expected that receipt of a
U34 grant will lead to the timely submission of an application (U01) for
support of the full-scale study, incorporating the elements developed under the
planning grant. .

Prospective applicants should note that funding of a U34
does not guarantee or imply funding for a subsequent U01 application.

Part 2. Multi-Center Clinical Study Cooperative Agreement
(U01). NIDDK will accept, peer review, and consider for funding applications
for investigator-initiated, multi-center clinical studies from U34 awardees
only, except when an exemption from this requirement has been obtained from
NIDDK. An applicant who can demonstrate that all the work required for a
submission of a multi-center clinical study application has been completed may
request an exemption from the prerequisite of holding a U34 award prior to
submitting the U01 application.

The materials developed in the U34 phase will allow the
applicant to initiate study staff training followed by study subject
recruitment soon after an expedited peer review and final NIDDK approval of the
clinical study application. In order not to delay the initiation of the study,
the peer review and award of the grant will be completed within four months of
the receipt of the application when possible. The purpose of the review of the
U01 is to insure that the applicant has accomplished the milestones established
in the U34 and to make sure that the scientific landscape has not changed and
that the proposed study is still of scientific importance and is feasible.

The U01 application should highlight any changes to the
protocol and all key decisions made during the U34 period, and should include
all DSMB recommendations. The application should include a clear discussion of
the power calculations and the feasibility of recruitment.

Cooperative Agreement: A support mechanism used when there
will be substantial Federal scientific or programmatic involvement.
Substantial involvement means that, after award, scientific or program staff
will assist, guide, coordinate, or participate in project activities.

Application Types Allowed

New
Renewal
Resubmission

The OER
Glossary and the SF 424 (R&R) Application Guide provide details on
these application types.

Funds Available and Anticipated Number of Awards

The number of awards is contingent upon NIH
appropriations, and the submission of a sufficient number of meritorious
applications.

Award Budget

Application budgets are not limited, but need to reflect
actual needs of the proposed project.

Award Project Period

The scope of the proposed project should determine the
project period. The maximum project period is 5 years.

NIH grants policies as
described in the NIH Grants Policy
Statement will apply to the applications
submitted and awards made in response to this FOA.

Section III. Eligibility Information

1. Eligible Applicants

Eligible Organizations

Higher Education Institutions:

Public/State Controlled Institutions of Higher Education

Private Institutions of Higher Education

The following types of Higher Education Institutions
are always encouraged to apply for NIH support as Public or Private
Institutions of Higher Education:

Applicant organizations must complete the following registrations
as described in the SF 424 (R&R) Application Guide to be eligible to apply
for or receive an award. Applicants must have a valid Dun and Bradstreet
Universal Numbering System (DUNS) number in order to begin each of the following
registrations.

All Program Directors/Principal Investigators (PD/PIs) must
also work with their institutional officials to register with the eRA Commons
or ensure their existing eRA Commons account is affiliated with the eRA Commons
account of the applicant organization.

All registrations must be completed by the application due date. Applicant
organizations are strongly encouraged to start the registration process at
least four (4) weeks prior to the application due date.

Eligible Individuals (Program Director/Principal Investigator)

Any individual(s) with the skills, knowledge, and resources
necessary to carry out the proposed research as the Program Director/Principal
Investigator (PD/PI) is invited to work with his/her organization to develop an
application for support. Individuals from underrepresented racial and ethnic
groups as well as individuals with disabilities are always encouraged to apply
for NIH support.

Only NIDDK clinical study planning (U34) grantees are
permitted to submit applications for clinical study cooperative agreements
awards (U01), unless an exemption from this requirement has been received from
NIDDK. An applicant who can demonstrate that all the work required for a
submission of a multi-center clinical study application has been completed may
request an exemption from the prerequisite of holding a U34 award prior to
submitting the U01 application. Information on the pre-approval process is available
at: http://www2.niddk.nih.gov/Research/ClinicalResearch/multicenterclinicalresearch.htm.

Applicant organizations may submit more than one application,
provided that each application is scientifically distinct.

NIH will not accept any application in response to this FOA
that is essentially the same as one currently pending initial peer review
unless the applicant withdraws the pending application. NIH will not accept any
application that is essentially the same as one already reviewed. Resubmission applications may be submitted, according to the NIH Policy on Resubmission
Applications from the SF 424 (R&R) Application Guide.

Section
IV. Application and Submission Information

1. Requesting an Application Package

Applicants must download the SF424 (R&R) application
package associated with this funding opportunity using the “Apply for Grant
Electronically” button in this FOA or following the directions provided at Grants.gov.

2. Content and
Form of Application Submission

It is critical that applicants follow the instructions in
the SF424
(R&R) Application Guide, except where instructed in this funding
opportunity announcement to do otherwise. Conformance to the requirements in
the Application Guide is required and strictly enforced. Applications that are
out of compliance with these instructions may be delayed or not accepted for
review.

Required and Optional Components

The forms package associated with this FOA includes all
applicable components, mandatory and optional. Please note that some
components marked optional in the application package are required for
application submission. Follow all instructions in the SF424 (R&R)
Application Guide to ensure you complete all appropriate “optional” components.

Page Limitations

All page limitations described in the SF424 Application
Guide and the Table of
Page Limits must be followed.

PHS 398 Research Plan Component

All instructions in the SF424 (R&R) Application Guide
must be followed, with the following additional instructions:

Research
Strategy: This section should include a discussion of the
significance of the problem being studied and the potential impact of the
results of the trial; a description of the study design, including power
analysis; a timeline for study conduct and a management plan for the conduct of
the trial; feasibility of recruitment; plans for subject randomization and
recruitment and retention; plans for monitoring of subject safety; and a description
of the data monitoring and data analysis plan. This section should highlight
any changes to the protocol made after the submission of the U34 application;
key decisions made during the U34 funding period; and any DSMB recommendations
made during the U34 funding period.

Inclusion of Women and Minorities: Applicants should
include a table describing the demographics of the available population at
every site.

Resource Sharing Plan

Individuals are required to comply with the
instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model
Organisms, and Genome Wide Association Studies (GWAS)) as provided in the SF424
(R&R) Application Guide.

Appendix

Do not use the appendix to circumvent page limits. Follow
all instructions for the Appendix as described in the SF424 (R&R)
Application Guide, with the following modifications:

The following items should be submitted as part of
the Appendix:

Complete study protocol

Documentation that the protocol has been submitted for IRB review

Template informed consent

Foreign Organizations

Foreign (non-US) organizations must follow policies
described in the NIH Grants
Policy Statement, and procedures for foreign organizations described
throughout the SF424 (R&R) Application Guide.

3. Submission Dates and Times

Part I. Overview Information contains information about Key Dates. Applicants are encouraged to submit in
advance of the deadline to ensure they have time to make any application
corrections that might be necessary for successful submission.

Organizations must submit applications via Grants.gov, the online portal to find and apply for grants
across all Federal agencies. Applicants must then complete the submission
process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants
administration.

Applicants
are responsible for viewing their application in the eRA Commons to ensure accurate
and successful submission.

Information on the submission process and a definition of
on-time submission are provided in the SF424 (R&R) Application Guide.

For assistance with your electronic application or for more information on the electronic submission
process, visit Applying
Electronically.

Important
reminders:All PD/PIs must include their eRA Commons ID in the Credential
fieldof the Senior/Key Person Profile Component of the SF 424(R&R) Application
Package. Failure to register in the Commons and to include a valid PD/PI
Commons ID in the credential field will prevent the successful submission of an
electronic application to NIH.

The applicant organization must ensure that the DUNS number it provides on the
application is the same number used in the organization’s profile in the eRA
Commons and for the Central Contractor Registration (CCR). Additional
information may be found in the SF424 (R&R) Application Guide.

Upon receipt, applications will be evaluated for
completeness by the Center for Scientific Review, NIH. Applications that are
incomplete will not be reviewed.

Requests of $500,000 or more for direct costs in any year

Applicants requesting $500,000 or more in direct costs in
any year (excluding consortium F&A) must contact NIH program staff at least 6 weeks before
submitting the application and follow the Policy on the Acceptance for Review
of Unsolicited Applications that Request $500,000 or More in Direct Costs as
described in the SF 424 (R&R) Application Guide.

Applicants must agree to the Cooperative Agreement Terms
and Conditions of Award.

Post Submission Materials

Applicants are required to follow the instructions for
post-submission materials, as described in NOT-OD-10-115, with the following modifications: Applicants may submit DSMB recommendations, if the DSMB
convenes after the application has been submitted.

Section
V. Application Review Information

1. Criteria

Only the review criteria described below will be considered
in the review process. As part of the NIH mission,
all applications submitted to the NIH in support of biomedical and behavioral
research are evaluated for scientific and technical merit through the NIH peer
review system.

For this particular announcement, note the following: The
NIDDK will certify that the applicant has achieved the milestones of the U34.
The applicant will not be allowed to proceed with the multi-center clinical
study cooperative agreement (U01) unless all materials required for training of
study staff and recruitment of study subjects have been developed. Therefore,
the review process will focus on evaluating whether the proposed study is still
of scientific importance and is feasible.

Overall Impact

Reviewers will provide an overall impact/priority score to
reflect their assessment of the likelihood for the project to exert a
sustained, powerful influence on the research field(s) involved, in
consideration of the following review criteria and additional review criteria
(as applicable for the project proposed).

Scored Review Criteria

Reviewers will consider each of the review criteria below in
the determination of scientific merit, and give a separate score for each. An
application does not need to be strong in all categories to be judged likely to
have major scientific impact. For example, a project that by its nature is not
innovative may be essential to advance a field.

Significance

Does the project address an important problem or a
critical barrier to progress in the field? If the aims of the project are
achieved, how will scientific knowledge, technical capability, and/or clinical
practice be improved? How will successful completion of the aims change the
concepts, methods, technologies, treatments, services, or preventative
interventions that drive this field?

Investigator(s)

Are the PD/PIs, collaborators, and other researchers
well suited to the project? If Early Stage Investigators or New Investigators,
or in the early stages of independent careers, do they have appropriate
experience and training? If established, have they demonstrated an ongoing
record of accomplishments that have advanced their field(s)? If the project is
collaborative or multi-PD/PI, do the investigators have complementary and
integrated expertise; are their leadership approach, governance and
organizational structure appropriate for the project? Does the application include a clear statement of the leadership and organization of the study,
including evidence that the principal investigator has experience in the
administration of a complex study?

Innovation

Does the application challenge and seek to shift
current research or clinical practice paradigms by utilizing novel theoretical
concepts, approaches or methodologies, instrumentation, or interventions? Are
the concepts, approaches or methodologies, instrumentation, or interventions
novel to one field of research or novel in a broad sense? Is a refinement,
improvement, or new application of theoretical concepts, approaches or
methodologies, instrumentation, or interventions proposed?

Approach

Are the overall strategy, methodology, and analyses
well-reasoned and appropriate to accomplish the specific aims of the project?
Are potential problems, alternative strategies, and benchmarks for success
presented? If the project is in the early stages of development, will the
strategy establish feasibility and will particularly risky aspects be
managed?

If the project involves clinical research, are the plans for 1) protection of
human subjects from research risks, and 2) inclusion of minorities and members
of both sexes/genders, as well as the inclusion of children, justified in terms
of the scientific goals and research strategy proposed? Is the experimental design adequate and does it address the following: translation of the clinical
question into a statistical hypothesis; endpoint(s) and data to be collected,
including relevance to the clinical and statistical hypothesis being tested;
sample size and duration of the study;

randomization, masking (if appropriate), and inclusion/exclusion
criteria; plans to standardize and monitor adherence to the clinical protocol,
and methods for standardization of procedures for data management and quality
control; availability of the requisite eligible patient pool; availability of
children, women and minority individuals as study participants and specific
recruitment and retention plans for their inclusion; the status of evidence
showing whether or not clinically important sex/gender and race/ethnicity
differences in the intervention effect are to be expected; plans for training
of study staff; plans for recruitment outreach and, as appropriate, follow-up
procedures to ensure collection of data at stated intervals; and data analysis
plan?

Environment

Will the scientific environment in which the work
will be done contribute to the probability of success? Are the institutional
support, equipment and other physical resources available to the investigators
adequate for the project proposed? Will the project benefit from unique
features of the scientific environment, subject populations, or collaborative
arrangements? Is the study population required for the proposed study
available?

Additional Review Criteria

As applicable for the project proposed, reviewers will
evaluate the following additional items while determining scientific and
technical merit, and in providing an overall impact/priority score, but will
not give separate scores for these items.

Protections for Human Subjects

For research that involves human subjects but does
not involve one of the six categories of research that are exempt under 45 CFR
Part 46, the committee will evaluate the justification for involvement of human
subjects and the proposed protections from research risk relating to their
participation according to the following five review criteria: 1) risk to
subjects, 2) adequacy of protection against risks, 3) potential benefits to the
subjects and others, 4) importance of the knowledge to be gained, and 5) data
and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or
more of the six categories of research that are exempt under 45 CFR Part 46,
the committee will evaluate: 1) the justification for the exemption, 2) human
subjects involvement and characteristics, and 3) sources of materials. For
additional information on review of the Human Subjects section, please refer to
the Human
Subjects Protection and Inclusion Guidelines.

Inclusion of Women, Minorities, and Children

When the proposed project involves clinical research,
the committee will evaluate the proposed plans for inclusion of minorities and
members of both genders, as well as the inclusion of children. For additional
information on review of the Inclusion section, please refer to the Human
Subjects Protection and Inclusion Guidelines.

Vertebrate Animals

The committee will evaluate the involvement of live
vertebrate animals as part of the scientific assessment according to the
following five points: 1) proposed use of the animals, and species, strains,
ages, sex, and numbers to be used; 2) justifications for the use of animals and
for the appropriateness of the species and numbers proposed; 3) adequacy of
veterinary care; 4) procedures for limiting discomfort, distress, pain and
injury to that which is unavoidable in the conduct of scientifically sound
research including the use of analgesic, anesthetic, and tranquilizing drugs
and/or comfortable restraining devices; and 5) methods of euthanasia and reason
for selection if not consistent with the AVMA Guidelines on Euthanasia. For
additional information on review of the Vertebrate Animals section, please
refer to the Worksheet
for Review of the Vertebrate Animal Section.

Biohazards

Reviewers will assess whether materials or procedures
proposed are potentially hazardous to research personnel and/or the
environment, and if needed, determine whether adequate protection is proposed.

Resubmissions

For Resubmissions, the committee will evaluate the
application as now presented, taking into consideration the responses to
comments from the previous scientific review group and changes made to the
project.

Renewals

For Renewals, the committee will consider the
progress made in the last funding period.

Revisions

Not Applicable

Additional Review Considerations

As applicable for the project proposed, reviewers will
consider each of the following items, but will not give scores for these items,
and should not consider them in providing an overall impact/priority score.

Applications from Foreign Organizations

Reviewers will assess whether the project presents
special opportunities for furthering research programs through the use of
unusual talent, resources, populations, or environmental conditions that exist
in other countries and either are not readily available in the United States or
augment existing U.S. resources.

Select Agent Research

Reviewers will assess the information provided in
this section of the application, including 1) the Select Agent(s) to be used in
the proposed research, 2) the registration status of all entities where Select
Agent(s) will be used, 3) the procedures that will be used to monitor
possession use and transfer of Select Agent(s), and 4) plans for appropriate
biosafety, biocontainment, and security of the Select Agent(s).

Reviewers will consider whether the budget and the
requested period of support are fully justified and reasonable in relation to
the proposed research.

2. Review and Selection Process

Applications will be evaluated for scientific and technical
merit by (an) appropriate Scientific Review Group(s) convened by the National Institute of Diabetes and Digestive and Kidney Diseases , in accordance with NIH peer
review policy and procedures, using the stated review
criteria. Review assignments will be shown in the eRA Commons.

As part of the scientific peer review, all applications:

May undergo a selection process in which only those applications
deemed to have the highest scientific and technical merit (generally the top
half of applications under review), will be discussed and assigned an overall impact/priority
score.

Will receive a written critique.

Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications
will compete for available funds with all other recommended applications . Following initial peer review, recommended applications will receive a second level of
review by the National Diabetes and Digestive and Kidney Diseases Advisory
Council. The following will be considered in making funding decisions:

Scientific and technical merit of the proposed project as
determined by scientific peer review.

Availability of funds.

Relevance of the proposed project to program priorities.

3. Anticipated Announcement and Award Dates

After the peer review of the application is completed, the
PD/PI will be able to access his or her Summary Statement (written critique)
via the eRA
Commons.

If the application is under consideration for funding, NIH
will request "just-in-time" information from the applicant as
described in the NIH Grants
Policy Statement.

A formal notification in the form of a Notice of Award (NoA) will be provided
to the applicant organization for successful applications. The NoA signed by
the grants management officer is the authorizing document and will be sent via
email to the grantee business official.

Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection
of an application for award is not an authorization to begin performance. Any
costs incurred before receipt of the NoA are at the recipient's risk. These
costs may be reimbursed only to the extent considered allowable pre-award costs.

The following special terms of award are in addition to, and
not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB)
administrative guidelines, U.S. Department of Health and Human Services (DHHS)
grant administration regulations at 45 CFR Parts 74 and 92 (Part 92 is
applicable when State and local Governments are eligible to apply), and other
HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this
program will be the cooperative agreement, an "assistance" mechanism
(rather than an "acquisition" mechanism), in which substantial NIH
programmatic involvement with the awardees is anticipated during the
performance of the activities. Under the cooperative agreement, the NIH purpose
is to support and stimulate the recipients' activities by involvement in and
otherwise working jointly with the award recipients in a partnership role; it
is not to assume direction, prime responsibility, or a dominant role in the
activities. Consistent with this concept, the dominant role and prime
responsibility resides with the awardees for the project as a whole, although
specific tasks and activities may be shared among the awardees and the NIH as
defined below.

The PD(s)/PI(s) will have the primary responsibility for:

1. Developing the research design and study protocol,
including definition of objectives and approaches, sample size and power
calculations, and establishing procedures for participant recruitment and
follow-up, data collection, quality control, interim data and safety
monitoring, final data analysis and interpretation, and publication of results.

2. Establishing a Steering Committee to implement,
coordinate and manage the project(s). Awardee(s) will name investigators to
serve as members on a Steering Committee and other subcommittees, as
appropriate, meeting periodically. Awardees will be required to accept and
implement the common protocol(s) and procedures approved by the Steering
Committee.

3. Implementing collection of data specified by the study
protocol, by the Steering Committee. For a multi-center study, each
awardee/site is required to ensure that data will be submitted expeditiously to
the Data Coordinating Center. Additionally, individual investigators/sites must
demonstrate the ability to implement the strategy specifically designed for
their individual study population.

4. Establishing procedures for data quality and
completeness. Awardees are responsible for ensuring accurate and timely
assessment of the progress of each study, including development of procedures
to ensure that data collection and management are: (1) adequate for quality
control and analysis; (2) for clinical trials, as simple as appropriate in
order to facilitate cooperation/referral of study participants by physicians to
avoid unnecessary expense; and (3) sufficiently staffed across the
participating institutions. For research involving multiple awards, a plan for
analysis of pooled data will be developed by the Steering Committee.

5. Submitting interim progress reports, when requested, to
the NIDDK Program Official including as a minimum, summary data on protocol
performance. For coordinated multiple awards or a multi-site single award, the
NIDDK Program Official may require additional information from individual
awardees/sites. Such reports are in addition to the required annual
noncompeting continuation progress report.

6. Establishing procedures, where applicable, for all
participating institutions in coordinated awards to comply with FDA regulations
for studies involving investigational agents or devices and to comply with the
requirements of 45 CFR Part 46 for the protection of human subjects, and the
NIH policy requirements for the inclusion of women, minorities and children.

7. Reporting of the study findings. The awardee(s) will
retain custody of and have primary rights to the data developed under these
awards, subject to the Government rights of access consistent with current HHS,
PHS and NIH policies. The awardee must also be adherent to Study Publication
and Presentation Policy. The NIDDK will have access to and may periodically
review all data generated under an award. NIDDK staff may co-author
publications of findings with awardees consistent with NIH and study policies.

8. Support or other involvement of industry or any other
third party in the study -- e.g., participation by the third party; involvement
of study resources or citing the name of the study or NIDDK support; or special
access to study results, primary data/summary information, or resources -- may
be advantageous and appropriate. However, except for licensing of patents or
copyrights, support or involvement of any third party is permitted only after
concurrence by NIDDK.

9. Study investigators are encouraged to publish and to
release publicly and disseminate results and other products of the study, in
accordance with study protocols and steering committee policies on
publications.

10. Maintaining confidentiality of information: The
awardee(s) will maintain the confidentiality of the information developed by
the investigators (i.e., protocols, data analysis, conclusions, etc.) as well
as proprietary information of a company collaborating with the study.

11. The NIDDK has established Central Biosample, Genetic,
and Data Repositories for the

archiving and storage of data and biosamples collected in
large, multi-site studies funded by NIDDK. The PI or his/her designee will
coordinate with the NIDDK Data Repository to prepare the collected data for
eventual archiving and distribution. In addition, if applicable, the PI or
his/her designee will work with the NIDDK Biosample Repository to coordinate
procedures for coding, shipping, processing, receipt, and storage of study
samples that are to be maintained in the Repository. All samples and data
transferred to the Repositories will be under the custodianship of the NIDDK,
although the study’s Steering Committee will have proprietary control of and
exclusive access to the samples and data for an agreed-upon period of time.
Subsequently samples and data will be available to the wider scientific
community in accordance with the NIH policy on Data Sharing (https://grants.nih.gov/grants/policy/data_sharing/ and, https://grants.nih.gov/grants/policy/data_sharing/data_sharing_guidance.htm#goals, and https://grants.nih.gov/grants/policy/data_sharing/data_sharing_faqs.htm).

12. The Food and Drug Administration Amendments Act of 2007
(FDAAA or US Public Law 110-85) was passed on September 27, 2007. The law
requires mandatory registration and results reporting for certain clinical
trials of drugs, biologics, and devices. If applicable, the PI or his/her
designee will perform the mandatory study registration and reporting of study
results to ClinicalTrials.gov. For more information about this law and
requirements for sponsors and/or investigators, visit the PRS and U.S. U.S.
Public Law 110-85 Information Page at http://prsinfo.clinicaltrials.gov/fdaaa.html

Awardees will retain custody of and have primary rights to
the data and software developed under these awards, subject to Government
rights of access consistent with current DHHS, PHS, and NIH policies.

NIH staff have substantial programmatic involvement that
is above and beyond the normal stewardship role in awards, as described below:

1. Serve as the contact point for all facets of the
scientific interaction with the awardee (s). As required for the coordination
of activities and to expedite progress, NIDDK may designate additional NIDDK
staff to provide advice to the awardee on specific scientific and/or analytic
issues. Such staff may include another Project Scientist or Analyst, who will
provide direct technical assistance to the awardees to optimize the conduct
and/or analysis of the study; or who may assist in the coordination of
activities across multiple sites.

2. For multi-center studies, participation in the Steering
Committee that oversees study conduct. The NIDDK Project Scientist or designee
will be a full participant and voting member of the Steering Committee and, if
applicable, subcommittees.

3. Serving as a resource to study investigators with respect
to other ongoing NIDDK activities that may be relevant to the study to
facilitate compatibility with the NIDDK missions and avoid unnecessary duplication
of effort.

4. Substantial involvement assisting in the design and
coordination of research activities for awardees as elaborated below:

a. Assisting by providing advice in the management and
technical performance of the investigations, coordinating required regulatory
clearances for investigational agents used in the study, which are held by
NIDDK. The NIDDK may reserve the right to cross file or independently file an
Investigational New Drug Application or an Investigational Device Exemption form
with the FDA.

b. The NIDDK Project Scientist or designee may coordinate
activities among awardees by assisting in the design, development, and
coordination of a common research or clinical protocol and statistical
evaluations of data; in the preparation of questionnaires and other data
recording forms; and in the publication of results.

d. The NIDDK Project Scientist or designee may be co-authors
on study publications. In general, to warrant co-authorship, NIDDK staff must
have contributed to the following areas: (a) design of the concepts or
experiments being tested; (b) performance of significant portions of the
activity; (c) participate in analysis and interpretation of study results and
(d) preparation and authorship of pertinent manuscripts.

In addition, a separate NIDDK Program Official identified in
the Notice of Award (NoA) will be responsible for the normal stewardship and
monitoring of the award including review and approval of all progress reports
and all budgetary decisions. Additional responsibilities include:

1. Interacting with the principal investigator(s) on
a regular basis to monitor study progress. Monitoring may include: regular
communications with the principal investigator and staff, periodic site visits,
observation of field data collection and management techniques, quality
control, fiscal review, and other relevant matters; as well as attendance at
Steering Committee, data safety and monitoring board, and related meetings. The
NIDDK retains, as an option, periodic review of progress by researchers not
involved with the study.

2. Reviewing and approving protocols prior to
implementation to insure they are within the scope of peer review, for safety
considerations, as required by Federal regulations.

3. The NIDDK Program Official will monitor protocol
progress, and may request that a protocol study be closed to accrual for
reasons including: (a) accrual rate insufficient to complete study in a timely
fashion; (b) accrual goals met early; (c) poor protocol performance; (d)
patient safety and regulatory concerns; (e) study results that are already
conclusive; and (f) emergence of new information that diminishes the scientific
importance of the study question. The NIDDK will not permit further
expenditures of NIDDK funds for a study after requesting closure except as
specifically approved by the NIDDK.

4. Making recommendations for continued funding
based on: a) overall study progress, including sufficient patient and/or data
accrual; b) cooperation in carrying out the research (e.g., attendance at
Steering Committee meetings, implementation of group decisions, compliance with
the terms of award and reporting requirements); and/or c) maintenance of a high
quality of research, which will allow pooling of data and comparisons across
multiple cooperative agreement awards for common data elements.

5. Appointment of a Data and Safety Monitoring Board
(DSMB) as appropriate; the NIDDK Program Official or their designee will serve
as the Executive Secretary and/or NIDDK program representative on the DSMB.

Areas of Joint Responsibility include:

1. Steering Committee.

A Steering Committee organized by the study investigator(s)
will be the main governing body of the study.

The Steering Committee has primary responsibility to design
research activities, establish priorities, develop common protocols and
manuals, questionnaires and other data recording forms, establish and maintain
quality control among awardees, review progress, monitor patient accrual,
coordinate and standardize data management, and cooperate on the publication
of results. Major scientific decisions regarding the core data will be
determined by the Steering Committee. The Steering Committee will document
progress in written reports to the NIDDK Program Official, and will provide
periodic supplementary reports upon request.

The Steering Committee will be composed of all Principal
Investigator(s), (including those of data coordinating /statistical centers, if
any) and co-investigators as deemed necessary, and the NIDDK Project Scientist.
The final structure of the Steering Committee and voting procedures will be
established at the first meeting. The NIDDK Project Scientist will have voting
membership on the Steering Committee, and as appropriate, its subcommittees.
The frequency of Steering Committee meetings will be dictated by a vote of the
members of the Steering Committee.

A Chairperson of the Steering Committee, other than the
NIDDK Project Scientist, will be selected by the NIDDK. The Chairperson
provides leadership to the Committee by conducting the Steering Committee meetings,
representing the study group to the External Oversight Committee established by
the NIDDK (see item D2 below) and by interacting closely with the awardees
during protocol development and implementation.

2. External Study Oversight.

An independent Data and Safety Monitoring Board will be
established by the NIDDK for Phase III clinical trials or other high risk
studies as appropriate. The Data and Safety Monitoring Board will review
interim results periodically and provide guidance to the NIDDK

Dispute Resolution:

Any disagreements that may arise in scientific or
programmatic matters (within the scope of the award) between award recipients
and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel
composed of three members will be convened. It will have three members: a
designee of the Steering Committee chosen without NIH staff voting, one NIH
designee, and a third designee with expertise in the relevant area who is
chosen by the other two; in the case of individual disagreement, the first
member may be chosen by the individual awardee. This special dispute resolution
procedure does not alter the awardee's right to appeal an adverse action that
is otherwise appealable in accordance with PHS regulation 42 CFR Part 50,
Subpart D and DHHS regulation 45 CFR Part 16.

A final progress report, invention
statement, and Financial Status Report are required when an award is
relinquished when a recipient changes institutions or when an award is
terminated.

The Federal Funding Accountability and Transparency Act of
2006 (Transparency Act), includes a requirement for awardees of Federal grants
to report information about first-tier subawards and executive compensation
under Federal assistance awards issued in FY2011 or later. All awardees of
applicable NIH grants and cooperative agreements are required to report to
the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants
Policy Statement for additional information on this reporting requirement.

Section VII. Agency Contacts

We encourage inquiries concerning this funding opportunity
and welcome the opportunity to answer questions from potential applicants.

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and
under Federal Regulations 42 CFR Part 52 and 45 CFR Parts 74 and 92.